Biomedical subjects

Yanping Zhang

Publications and source records attributed to Yanping Zhang.

At least 37 records · Page 2Linked to original sources

PubMed2006

[Fhit expression and its relationship with apoptosis and prognosis in nasal and paranasal sinus carcinomas].

OBJECTIVE: To assess the protein expression of Fhit and its correlation with spontaneous apoptosis, tumor clinicopathological parameters and prognosis in nasal and paranasal sinus carcinomas. METHOD: Forty-eight patients with NPSC treated by radical operations from 1991 to 2000 were studied retrospectively. Patients included 23 female and 25 male ranging in age from 20 to 71 years. Spontaneous apoptotic cells were visualized by TUNEL accompanied by HE and PI stain. Immunohistochemistry using SP method was used to assess the expression of Fhit. RESULT: The loss of expression of Fhit was found in 26 patients (54.17%, 26/48). Comparing with abutting non-neoplastic tissue, reduced expression of Fhit was found in 16 (16/29, 55.17%) patients. The adenoid cystic carcinoma showed stronger expression of Fhit than squamous cell carcinomas (P <0.05). The expression of Fhit correlated positively with apoptosis index (r = 0.379, P < 0.01). Patients with positive expression of Fhit had much better prognosis than those with abnormal expression (P < 0.05). CONCLUSION: The reduced expression of Fhit may be associated with carcinogenesis and prognosis of nasal and paranasal sinus carcinomas. It could be the tumor suppressor gene and realize its function through accelerating apoptosis in this kind of neoplasm. Fhit expression may provide a novel predictive indicator for disease-free survival after surgical resection and postoperative radiochemotherapy in nasal and paranasal sinus carcinomas.

Acid Anhydride Hydrolases↗

PubMed2005

Physical and chemical stability of pemetrexed solutions in plastic syringes.

BACKGROUND: Pemetrexed is a multitargeted antifolate antineoplastic agent that is indicated for single-agent use in advanced or metastatic non-small-cell lung cancer and in combination with cisplatin for the treatment of malignant pleural mesothelioma not treatable by surgery. Currently, there is no information on the long-term stability of pemetrexed solutions beyond 24 hours. OBJECTIVE: To evaluate the stability of pemetrexed reconstituted with NaCl 0.9% injection to a concentration of 25 mg/mL and packaged in polypropylene syringes. METHODS: Triplicate samples of reconstituted pemetrexed 25 mg/mL were packaged in 20-mL polypropylene syringes and evaluated for physical and chemical stability performed initially and over 2 days of storage at 23 degrees C and over 31 days of storage at 4 degrees C. Physical stability was assessed using turbidimetric and particulate measurement, as well as visual observation. Chemical stability was evaluated by HPLC. RESULTS: The reconstituted pemetrexed solutions remained physically and chemically stable throughout the respective study periods, with no precipitation or color change and little or no loss of pemetrexed. CONCLUSIONS: Pemetrexed reconstituted with NaCl 0.9% to a concentration of 25 mg/mL packaged in polypropylene syringes was found to be stable for 2 days at room temperature and 31 days refrigerated.

Antimetabolites, Antineoplastic↗

PubMed2005

Gap junction-mediated intercellular biochemical coupling in cochlear supporting cells is required for normal cochlear functions.

Dysfunction of gap junctions (GJs) caused by mutations in connexin26 (Cx26) and Cx30 accounts for nearly half of all cases of hereditary nonsyndromic deafness cases. Although it is widely held that GJs connecting supporting cells in the organ of Corti mainly provide ionic pathways for rapid removal of K+ around the base of hair cells, the function of GJs in the cochlea remains unknown. Here we show that GJs were not assembled in the supporting cells of the organ of Corti until 3 days after birth in mice and then gradually matured to connect supporting cells before the onset of hearing. In organotypic cochlear cultures that were confirmed to express GJs, GJs mediated the propagation of intracellular Ca2+ concentration waves in supporting cells by allowing intercellular diffusion of inositol 1,4,5-trisphosphate. We found that a subset of structurally mild Cx26 mutations located at the second transmembrane region (V84L, V95M, and A88S) and a Cx30 mutation located at the first cytoplasmic segment (T5M) specifically affect the intercellular exchange of larger molecules but leave the ionic permeability intact. Our results indicated that Cx26 and Cx30 mutations that are linked to sensorineural deafness retained ionic coupling but were deficient in biochemical permeability. Therefore, GJ-mediated intercellular exchange of biochemically important molecules is required for normal cochlear functions.

Animals↗

PubMed2005

Regulation of polarized extension and planar cell polarity in the cochlea by the vertebrate PCP pathway.

The mammalian auditory sensory organ, the organ of Corti, consists of sensory hair cells with uniformly oriented stereocilia on the apical surfaces and has a distinct planar cell polarity (PCP) parallel to the sensory epithelium. It is not certain how this polarity is achieved during differentiation. Here we show that the organ of Corti is formed from a thicker and shorter postmitotic primordium through unidirectional extension, characteristic of cellular intercalation known as convergent extension. Mutations in the PCP pathway interfere with this extension, resulting a shorter and wider cochlea as well as misorientation of stereocilia. Furthermore, parallel to the homologous pathway in Drosophila melanogaster, a mammalian PCP component Dishevelled2 shows PCP-dependent polarized subcellular localization across the organ of Corti. Taken together, these data suggest that there is a conserved molecular mechanism for PCP pathways in invertebrates and vertebrates and indicate that the mammalian PCP pathway might directly couple cellular intercalations to PCP establishment in the cochlea.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Use of oxidoreduction potential as an indicator to regulate 1,3-propanediol fermentation by Klebsiella pneumoniae.

Anaerobic fermentation was relatively difficult to optimize due to lack of monitoring parameters. In this paper, a new method was reported using extracellular oxidoreduction potential (ORP) to monitor 1,3-propanediol (1,3-PD) biosynthesis process by Klebsiella pneumoniae. In batch fermentation, cell growth, 1,3-propanediol production and by-products distribution were studied at four different ORP levels: 10, -140, -190 and -240 mV. From the results, the ORP level of -190 mV was preferable, which resulted in fast cell growth and high 1,3-propanediol concentration. The NAD+/NADH ratio was determined at different ORP levels, and a critical NAD+/NADH ratio of 4 was defined to divide fermentation environments into two categories: relatively oxidative environment (NAD+/NADH>4) and relatively reductive environment (NAD+/NADH<4). The former was correlative with high 1,3-propanediol productivity and high specific growth rate. The mechanism of ORP regulation was discussed. It is suggested that ORP regulation of fermentation might be due to its influence on the ratio of NAD+/NADH, which determined metabolic flux. Furthermore, a batch fermentation of modulating ORP following a profile in different levels corresponding to different fermentation stage was tested. The 1,3-PD concentration was 22.3% higher than that of constant ORP fermentation at -190 mV. Therefore, ORP is a valuable parameter to monitor and control anaerobic fermentation production.

Anaerobiosis↗

PubMed2005

Nuclear import of the stem-loop binding protein and localization during the cell cycle.

A key factor involved in the processing of histone pre-mRNAs in the nucleus and translation of mature histone mRNAs in the cytoplasm is the stem-loop binding protein (SLBP). In this work, we have investigated SLBP nuclear transport and subcellular localization during the cell cycle. SLBP is predominantly nuclear under steady-state conditions and localizes to the cytoplasm during S phase when histone mRNAs accumulate. Consistently, SLBP mutants that are defective in histone mRNA binding remain nuclear. As assayed in heterokaryons, export of SLBP from the nucleus is dependent on histone mRNA binding, demonstrating that SLBP on its own does not possess any nuclear export signals. We find that SLBP interacts with the import receptors Impalpha/Impbeta and Transportin-SR2. Moreover, complexes formed between SLBP and the two import receptors are disrupted by RanGTP. We have further shown that SLBP is imported by both receptors in vitro. Three sequences in SLBP required for Impalpha/Impbeta binding were identified. Simultaneous mutation of all three sequences was necessary to abolish SLBP nuclear localization in vivo. In contrast, we were unable to identify an in vivo role for Transportin-SR2 in SLBP nuclear localization. Thus, only the Impalpha/Impbeta pathway contributes to SLBP nuclear import in HeLa cells.

Alanine↗

PubMed2005

Transcription of brain creatine kinase in U87-MG glioblastoma is modulated by factor AP2.

Our previous studies established in U87-MG glioblastoma cells that elevated cAMP increased transcription of the endogenous as well as a transiently-transfected brain creatine kinase (CKB) gene, despite the absence of a cAMP response element (CRE) in the CKB proximal promoter. This report employed transfection to show that the transcription of CKB in U87 cells is induced by transcription factor AP2alpha, which is known to be activated by cAMP. Dominant-negative forms of AP2alpha not only prevented the AP2alpha-mediated activation of CKB but also blocked the cAMP-mediated increase in CKB transcription caused by forskolin treatment. The mutation of the four potential AP2 elements within the CKB proximal promoter showed that induction of CKB by AP2 was mediated principally through the AP2 element located at -50 bp in the promoter. Electromobility shift assays revealed a protein in U87 nuclear extracts that bound to a consensus AP2alpha element as well as to the (-50) AP2 element in CKB. Interestingly, the CKB (-50) AP2 element contains GCCAATGGG which also bound NF-Y, the CCAAT-binding protein, suggesting that interplay between AP2 and NF-Y may modulate CKB transcription. This is the first report of a role for AP2 in the regulation of CKB transcription and of an AP2 element within which an NF-Y site is located.

Base Sequence↗

PubMed2005

Design, synthesis, and preliminary evaluation of gabapentin-pregabalin mutual prodrugs in relieving neuropathic pain.

As a part of a program for the development of specific analgesics in relieving neuropathic pain, the purpose of the present study was to investigate a new concept that involves the conjugation of two drugs, gabapentin and pregabalin, as mutual prodrugs using a chemical modification approach. A series of gabapentin-pregabalin diester compounds were synthesized using linear or branch bis-hydroxyl linkers. Their pharmacological properties for treating neuropathic pain were investigated in a rat model of chronic sciatic nerve constriction injury (CCI). In-vivo evaluation demonstrated that 1a and 1b composed of two gabapentin molecules as well as 3a composed of gabapentin and pregabalin with the short linear linker, were effective in reversing tactile allodynia in CCI rats. Compounds with longer or side-branched linkers showed lower efficiencies and severe adverse effects.

Amines↗

PubMed2005

Hypoxia promotes interleukin-6 and -8 but reduces interleukin-10 production by placental trophoblast cells from preeclamptic pregnancies.

OBJECTIVE: Placental hypoxia and altered placental cytokine productions have been considered to play a significant role in the pathophysiology of preeclampsia. The objective of this study was to determine whether hypoxia could modify interleukin (IL)-6, IL-8, and IL-10 production by placental trophoblast cells (TCs) from normal and preeclamptic (PE) pregnancies. METHODS: Placentas were obtained from nine normal and nine PE pregnancies immediately after delivery. Placental TCs were isolated and cultured under normoxic (21% O(2)/air) and hypoxic (2% O(2)/5% CO(2)/92% N(2)) conditions for 48 hours. TC productions of IL-6, IL-8, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). Unpaired t tests or paired t test was used for the statistical analysis and data are expressed as means +/- SE (pg/mug cellular protein). A P value less than .05 was considered statistically significant. RESULTS: PE-TCs produced significantly more IL-6, IL-8, and IL-10 than those of normal-TCs when they were cultured under normoxic condition, P < .05. Both normal-TCs and PE-TCs produced more IL-6 and IL-8 when they were cultured under hypoxic conditions. Hypoxia reduced IL-10 production by PE-TCs, but had no effect on IL-10 production by normal-TCs. CONCLUSIONS: Hypoxia promotes both IL-6 and IL-8 but reduces IL-10 production by placental TCs from PE pregnancies.

Adult↗

PubMed2005

Effects of peroxynitrite and superoxide radicals on endothelial monolayer permeability: potential role of peroxynitrite in preeclampsia.

OBJECTIVE: Increased endothelial permeability is associated with increased oxidative stress in the maternal vasculature in women with preeclampsia. This study was to determine if oxidative stress elicited by peroxynitrite could lead to an increase in endothelial permeability. METHODS: Endothelial oxidative stress was produced by adding 3-morpholinosydnonimine (SIN-1, a peroxynitrite generator) to the cell culture. Confluent endothelial cells (ECs) grown in cell culture inserts were treated with SIN-1 at a concentration of 0.5 mM alone or in combination with MnTMPyP (a peroxynitrite scavenger) or superoxide dismutase (SOD). EC permeability was determined by measuring EC electrical resistance (ER) and horseradish peroxide (HRP) leakage. Data are presented as means +/- SE and analyzed by analysis of variance (ANOVA). Junctional protein expression and distribution for vascular endothelial (VE)-cadherin, occludin, and phosphorylated focal adhesion kinase (FAK) at tyrosine 397 [pY397] were examined by fluorescent staining of ECs. RESULTS: First, ER was significantly reduced and HRP leakage was significantly increased in ECs treated with SIN-1 compared to those in control cells, ER: 26.97 +/- 1.41 versus 42.27 +/- 0.40 Omega.cm2, P <.01; HRP: 0.26 +/- 0.07 versus 0.02 +/- 0.01 OD 470 nm, P <.01, respectively. Second, cells treated with SIN-1 showed formation of gaps and disorganized VE-cadherin and occludin distribution at cell contact regions. FAK[pY397] expression was completely lost in cells treated with SIN-1. Finally, these functional and morphologic changes in ECs induced by SIN-1 were blocked in cells pretreated with MnTMPyP and SOD. CONCLUSIONS: Disorganization of junctional proteins and dephosphorylation of FAK[pY397] may account for the increased endothelial permeability induced by oxidative stress associated with preeclampsia.

Cell Membrane Permeability↗

PubMed2005

Increased phospholipase A2 and thromboxane but not prostacyclin production by placental trophoblast cells from normal and preeclamptic pregnancies cultured under hypoxia condition.

In this study we determined whether hypoxia could promote vasoactivator thromboxane (TX) and prostacyclin (PGI2) as well as phospholipase A2 (PLA2) production by placental trophoblast cells (TCs) from normal and preeclamptic (PE) pregnancies. Placentas were obtained immediately after delivery from normal (n=9) and preeclamptic (n=9) pregnancies. TCs were isolated by dispase digestion of villous tissue and purified by Percoll gradient centrifugation. TCs (5x10(6) cells/well) were cultured with Dulbecco's Modified Eagles Medium (DMEM) under hypoxia condition (2% O2/5% CO2/93% N2) for 48 h. TCs cultured under normoxia condition (5% CO2/air) were used as control. Culture medium was collected at the end of incubation. Productions for TX, PGI2 and PLA2 were measured by ACE competitive enzyme immunoassay (EIA). Comparisons were made using the Mann-Whitney U test or paired t-test and the data are expressed as mean+/-SE (pg/microg cellular protein). Significance was set at a p-value of <0.05. We found: (1) PE-TCs produced more TXB2 and PLA2 than normal-TCs under normoxia conditions, TXB2: 4.33+/-1.03 vs. 1.84+/-0.29 pg/microg protein, p<0.05; PLA2: 0.38+/-0.08 vs. 0.21+/-0.03 pg/microg protein, p<0.05, respectively. (2) Hypoxia promoted both PE- and normal-TCs to generate more TXB2 and PLA2, TXB2: 6.36+/-1.72 vs. 3.05+/-0.45 pg/microg; PLA2: 0.52+/-0.10 vs. 0.30+/-0.04 pg/microg, respectively. (3) No change in 6-keto PGF1alpha production was observed for normal-TCs or PE-TCs when compared under normoxia vs. hypoxia condition, normal-TCs: 0.20+/-0.05 vs. 0.21+/-0.05 pg/microg; PE-TCs: 0.38+/-0.05 vs. 0.36+/-0.04 pg/microg, respectively. We concluded that hypoxia promotes both PLA2 and TX, but not PGI2, production by placental trophoblast cells cultured under hypoxia condition. These results suggest that increased PLA2 release may alter the arachidonic acid cascade and promote TX synthesis. Relative hypoxia could contribute to the increase in TX production and result in vasoconstriction in placental vasculature in preeclampsia.

6-Ketoprostaglandin F1 alpha↗

PubMed2005

Removal of estrone and 17beta-estradiol from water by adsorption.

Endocrine disrupting chemicals (EDCs) are the focus of current environment concern, as they can cause adverse health effects in an intact organism, or its progeny, subsequent to endocrine function. The paper reports on the removal of estrone (E1) and 17beta-estradiol (E2) from water through the use of various adsorbents including granular activated carbon (GAC), chitin, chitosan, ion exchange resin and a carbonaceous adsorbent prepared from industrial waste. The results show that the kinetics of adsorption were adsorbent and compound-dependent, with equilibration being reached within 2 h for a waste-derived carbonaceous adsorbent to 71 h for an ion-exchange resin for E1, and within 7 h for the waste-derived carbonaceous adsorbent to 125 h for GAC for E2. Of all the adsorbents tested, the carbonaceous adsorbent showed the highest adsorption capacity, with a maximum adsorption constant of 87500 ml/g for E1 and 116000 ml/g for E2. The GAC also had a very high adsorption capacity for the two compounds, with a maximum adsorption constant of 9290 ml/g for E1 and 12200 ml/g for E2. The effects of some fundamental environmental parameters including adsorbent concentration, pH, salinity and the presence of humic acid and surfactant on adsorption were studied. The results show that adsorption capacity of activated carbon was decreased with an increase in adsorbent concentration and by the presence of surfactant and humic acid. The results have demonstrated excellent performance of a waste derived adsorbent in removing E1 and E2 from water, and indicated the potential of converting certain solid waste into useful adsorbents for pollution-control purposes.

Adsorption↗

PubMed2005

Low-planned suicides in China.

BACKGROUND: Acts of suicide differ widely in the amount of planning preceding the act. Correlates of completed suicide in China identified in a previous investigation were re-examined to identify those that may be especially relevant to low-planned (impulsive) and high-planned suicidal behavior. The association of planning and method in completed suicide was also assessed. METHOD: A psychological autopsy study of 505 suicide decedents aged > or = 18 years sampled to be representative of suicides in China was conducted. Multinomial regression analyses compared three levels of suicide planning (low, intermediate, high). RESULTS: Women and younger individuals were more likely to carry out low-planned and intermediate-planned than high-planned acts of suicide. Greater acute stress distinguished low-planned from high-planned suicides. Ingestion of pesticides stored in the home was a more commonly employed method in low-planned than high-planned suicides. CONCLUSIONS: Low-planned suicides are more common in women, in younger individuals, and among those who are experiencing acute stress. Prevention strategies targeted at restricting access to pesticides may preferentially lower the rate of low-planned suicides.

Adolescent↗

PubMed2005

Survivin expression and its relationship with apoptosis and prognosis in nasal and paranasal sinus carcinomas.

CONCLUSIONS: The inverse correlation found in this study between survivin expression and the level of spontaneous apoptosis in nasal and paranasal sinus carcinoma (NPSC) suggests that survivin may play an important role in the tumorigenesis of NPSC. Survivin expression may provide a novel predictive indicator for disease-free survival after surgical resection and postoperative radiochemotherapy in NPSC. OBJECTIVES: NPSC is the third commonest neoplasm in otolaryngology. Little is known about the distribution of inhibitors of apoptosis in NPSC and how they correlate with the prognoses of patients. The objectives of this study were to assess the protein expression of a new inhibitor of apoptosis, survivin, and its correlation with spontaneous apoptosis, tumor clinicopathological parameters and prognosis in NPSC. MATERIAL AND METHODS: A total of 48 patients (23 females, 25 males; age range 20-71 years) with NPSC treated by means of radical operations between 1991 and 2000 were studied retrospectively. Spontaneous apoptotic cells were visualized by means of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling in combination with hematoxylin-eosin and propidium iodide staining. Immunohistochemistry using the streptavidin-peroxidase method was used to assess the expression of survivin. RESULTS: Survivin expression was positive in 23/48 samples (47.92%) but no staining was present in normal tissues adjacent to the tumors. The expression of survivin correlated negatively with the apoptotic index (r = - 0.393; p = 0.006). Patients with positive expression of survivin had a lower apoptotic index than those with negative expression (p < 0.05). The expression of survivin in advanced-stage tumors (T3 + T4) was higher than that in early ones (T1 + T2) (p < 0.05). Patients with negative expression of survivin had a much better prognosis than those with positive expression (p = 0.0346). Multivariate analyses revealed that expression of survivin and histological type were independent prognostic factors for overall survival.

Adult↗

PubMed2005

Surgical management of invasive breast cancer: a 5-year prospective study of treatment in the Australian Capital Territory and South-Eastern New South Wales.

BACKGROUND: Breast cancer is a major health problem in Australia. The aim of the present report is to evaluate the surgical management of invasive breast cancers in our region. METHODOLOGY: As part of a multidisciplinary quality assurance project, data were collected for the majority of breast cancers treated in our region between July 1997 and June 2002. Participants included surgeons, medical and radiation oncologists, pathologists and general practitioners. RESULTS: Over the 5-year period, 1069 invasive breast cancers were treated. Mastectomy (52%) was more common than breast conservation. For cancers less than 2 cm in diameter (61%), breast conservation was achieved in 62%. High nuclear grade cancers (27%) resulted in mastectomy in 60%. This treatment pattern was the same for patients living in urban and rural areas and in all age groups. Those patients requiring two or more operations (30%) to achieve surgical clearance still had a 33% rate of breast conservation. Over the last 5 years there has been an increase in sentinel node biopsies (16 sentinel node biopsies during 1998-1999; 64 during 2001-2002) and axillary dissections started to decrease. A small group has had no axillary node biopsy or dissection, mainly patients over 70 years of age. Multimodality treatments increased over the 5-year period of our study with the use of postoperative radiotherapy increasing from 60% to 65% and chemotherapy from 36% to 55%. CONCLUSIONS: The project has mapped treatment trends for breast cancer in our region and documented the implementation of new treatment methods as well as the increasing use of multidisciplinary management, multimodality treatment and the implementation of best practice guidelines.

Australian Capital Territory↗

PubMed2005

Cochlear gap junctions coassembled from Cx26 and 30 show faster intercellular Ca2+ signaling than homomeric counterparts.

The importance of connexins (Cxs) in cochlear functions has been demonstrated by the finding that mutations in Cx genes cause a large proportion of sensorineural hearing loss cases. However, it is still unclear how Cxs contribute to the cochlear function. Recent data (33) obtained from Cx30 knockout mice showing that a reduction of Cx diversity in assembling gap junctions is sufficient to cause deafness suggest that functional interactions of different subtypes of Cxs may be essential in normal hearing. In this work we show that the two major forms of Cxs (Cx26 and Cx30) in the cochlea have overlapping expression patterns beginning at early embryonic stages. Cx26 and Cx30 were colocalized in most gap junction plaques in the cochlea, and their coassembly was tested by coimmunoprecipitation. To compare functional differences of gap junctions with different molecular configurations, homo- and heteromeric gap junctions composed of Cx26 and/or Cx30 were reconstituted by transfections in human embryonic kidney-293 cells. The ratio imaging technique and fluorescent tracer diffusion assays were used to assess the function of reconstituted gap junctions. Our results revealed that gap junctions with different molecular configurations show differences in biochemical coupling, and that intercellular Ca(2+) signaling across heteromeric gap junctions consisting of Cx26 and Cx30 was at least twice as fast as their homomerically assembled counterparts. Our data suggest that biochemical permeability and the dynamics of intercellular signaling through gap junction channels, in addition to gap junction-mediated intercellular ionic coupling, may be important factors to consider for studying functional roles of gap junctions in the cochlea.

Animals↗

PubMed2004

Palonosetron HCl compatibility and stability with doxorubicin HCl and epirubicin HCl during simulated Y-site administration.

BACKGROUND: Palonosetron HCl is a selective 5-HT3 receptor antagonist used for the prevention of chemotherapy-induced nausea and vomiting. Palonosetron HCl may be administered with other drugs by Y-site administration, including doxorubicin HCI and epirubicin HCI. Consequently, stability and compatability information are needed to verify the acceptability of such Y-site administration. OBJECTIVE: To evaluate the physical and chemical stability of undiluted palonosetron HCl 50 microg/mL with doxorubicin HCl 1 mg/mL and epirubicin HCl 0.5 mg/mL during simulated Y-site administration. METHODS: Triplicate samples of palonosetron HCl with each of the anthracycline chemotherapy drugs were tested. Samples were stored and evaluated for up to 4 hours at room temperature near 23 degrees C. Physical stability was assessed using turbidimetric and particulate measurement, as well as visual inspection. Chemical stability was assessed by HPLC. RESULTS: All of the admixtures were clear and red-orange when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and remained low throughout the study. The drug concentration was unchanged in any of the samples throughout the study. CONCLUSIONS: Palonosetron HCl is physically and chemically stable with doxorubicin HCl and epirubicin HCl during simulated Y-site administration of these drugs over 4 hours at ambient room temperature.

Drug Interactions↗

PubMed2004

Essential role of ribosomal protein L11 in mediating growth inhibition-induced p53 activation.

The ribosomal protein L11 binds to and suppresses the E3 ligase function of HDM2, thus activating p53. Despite being abundant as a component of the 60S large ribosomal subunit, L11 does not induce p53 under normal growth conditions. In search of mechanisms controlling L11-HDM2 interaction, we found that the induction of p53 under growth inhibitory conditions, such as low dose of actinomycin D or serum depletion, can be significantly attenuated by knocking down L11, indicating the importance of L11 in mediating these growth inhibitory signals to p53. We show that L11 is not regulated by transcription or protein stability and its level remains relatively constant during serum starvation. However, serum starvation induces translocation of L11 from the nucleolus to the nucleoplasm, where it participates in a complex with HDM2. We propose that the nucleolus acts as a barrier to prevent L11 interacting with HDM2 during normal growth. Growth inhibition, presumably through suppression of rRNA production in the nucleolus, facilitates translocation of L11 to the nucleoplasm, thus activating p53 through inhibiting HDM2.

Amino Acid Sequence↗